The treatment of inflammatory diseases of the mouth is difficult. Patients so afflicted often require treatment with agents that are potentially toxic when given systemically to control the disease activity. Moreover, diseases such as oral lichen planus, pemphigus, pemphigoid, aphthous stomatitis, erythema multiforme, and idiopathic stomatitis are disorders in which spontaneous remissions are rare. Means of treating such diseases without undue exposure of the patient to systemic effects of powerful therapeutic agents is desirable.
Treatment with topical corticosteroids as presently formulated and administered has significant limitations. Existing commercially available compositions are usually supplied as creams, gels, or ointments that are intended for cutaneous applications. Such preparations are not readily acceptable to patients for use on the mucosa. The prior art compositions must be applied frequently (up to six times a day). Furthermore, the compositions are not readily applied to the areas of the oral cavity that are difficult to reach. Furthermore, treatment with steroids causes increased susceptibility to fungal infections of the mouth. This complication is especially common in patients suffering from oral lichen planus, a condition in which Candida is found to colonize mouth lesions in 25% of the patients.
Aqueous preparations of steroids are known. Kenalog (TM) 10 Injection is an aqueous suspension used for intradermal, intra-articular, and intrabursal administration. The suspension is not appropriate for use intravenously or intramuscularly, and there is no suggestion that the suspension can be used as a mouthwash or swish for treatment of inflammatory diseases of the oral cavity. Aristospan (TM) is also used as a suspension for intralesional administration and is available as a cream for topical application. Similarly, Kenalog-H (TM) cream is applied topically to the skin. Use of these preparations has an increased susceptibility of the patient to fungal infections as an untoward effect. A dermatological cream preparation containing an antifungal, nystatin, and a steroid, triamcinolone acetonide, is available under the trade name Mycolog II. Being a cream preparation, it is not appropriate for use as a mouthwash. Preparations containing a suspension of nystatin for use as a swish (mouthwash) are available. However, those preparations do not contain any anti-inflammatory steroid as an active agent.
No teaching of use of mouthwashes containing both antifungal agents and anti-inflammatory agents has been found in the patent literature. Segal, et al, in U.K. Patent Application GB 2,167,296 describe a variety of pharmaceutical compositions containing glycyrrhizin for topical applications. That patent publication indicates that the glycyrrhizin, a necessary component of the compositions taught therein, formed stable aqueous gels. A gel containing triamcinolone for treatment of oral ulcerations is described in one example. In another example a gel containing nystatin for treating oral candidiasis is described. U.S. Pat. No. 4,101,652 to Bonati teaches complexes of saponins with sterols for use in treating inflammation. The complex having a saponin as an essential moiety is necessary to that invention. Although use of the complexes in dentifrices is disclosed, no teaching of preparations for use as mouthwashes is seen therein. U.S. Pat. No. 4,933,172 to Clark, et al. teaches the nonsteroidal anti-inflammatory agent 2-(2,6 dichloro-3 methylphenylamino)benzoic acid for use in treating gingivitis. One of the formulations taught is a mouthwash. U.S. Pat. No. 4,835,142 to Suzuki, et al. describes powdery compositions for application to the mucosa of the oral or nasal cavity. U.S. Pat. No. 4,782,047 to Benjamin, et al. teaches use of anti-inflammatory steroids as nasal sprays. No method for treating oral infections using mouthwashes is disclosed therein.
R. A. Cawson ("Treatment of Oral Lichen Planus with Betamethasone", British Medical Journal, (Jan. 13, 1968)) teaches the use of betamethasone pellets to treat oral lichen planus. Use of hydrocortisone pellets was also tried. The betamethasone pellets were efficacious. Hydrocortisone pellets were rarely effective, even when combined with tetracycline mouthwashes.
Rothwell and Spektor ("Palliation of Radiation-related Mucositis", Special Care in Dentistry, (January-February 1990)) discloses a method of treating patients undergoing irradiation therapy comprising prophylactic use of mouth rinse with a preparation containing tetracycline, 500 mg; nystatin, 1,200,000 U; hydrocortisone, 100 mg; and diphenhydramine elixir, 10 ml. to make a solution of 25 ml. It is taught that tetracycline is unstable in solution and was, therefore, dispensed as a separate solution. It is not clear if the tetracycline was mixed with the other active agents just before using the rinse. However, the method taught therein was not used to treat existing, chronic inflammatory problems such as oral lichen planus.